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The following information helps you to find FDA Alerts and Pharmacist’s Applications to Practice quickly and easily. In cooperation with the Food and Drug Administration (FDA), and as a service to our members, HOPA periodically distributes information about newly approved therapies for cancer patients from FDA’s Office of Oncology Drug Products Director, Dr. Richard Pazdur to inform oncologists and professionals in oncology-related fields in a timely manner. Links to product labels will take you to relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, HOPA does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

Along with HOPA’s Publications Committee, members also review new drug updates and provide analysis and research on the application of these new drugs or indications. Pharmacist’s Applications to Practice, or PAP, are listed after drugs that include the additional analysis. If you are interested in helping the Publications Committee with creating a Pharmacist's Application to Practice, please contact Jeff Price at jprice@hoparx.org.

You can also find additional information on FDA Alerts and Updates by listening to FDA Drug Safety Podcasts.


March 29, 2018–Blinatumomab (Blincyto®, Amgen Inc.) granted accelerated approval for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%  (with Pharmacist's Applications to Practice)

July 11, 2017–Blinatumomab (BLINCYTO®, Amgen Inc.) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children (with Pharmacists's Applications to Practice)


March 29, 2018, with PAP

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf

On March 29, 2018, the Food and Drug Administration granted accelerated approval to blinatumomab (Blincyto®, Amgen Inc.) for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.

Approval was based on the open label, multicenter, single-arm BLAST trial (NCT 01207388) that included 86 patients who were at least 18 years of age, had received at least 3 chemotherapy blocks of standard ALL therapy, were in complete hematologic remission (defined as < 5% blasts in bone marrow, absolute neutrophil count > 1 Gi/L, platelets > 100 Gi/L) and had MRD at a level of greater than or equal to 0.1% using an assay with a minimum sensitivity of 0.01%. Blinatumomab was administered at a constant dose of 15 mcg/m2/day (equivalent to the recommended dose of 28 mcg/day) intravenously for all treatment cycles. Patients received up to 4 cycles of treatment. Following treatment with blinatumomab, 45 out of 61 (74%) patients in CR1 and 14 out of 25 (56%) patients in CR2 underwent allogeneic hematopoietic stem cell transplantation in continuous hematologic complete remission.

Efficacy was based on both achievement of undetectable MRD within one cycle of blinatumomab treatment and hematological relapse-free survival (RFS). The assay used to assess MRD response had a sensitivity of 0.01% for 6 patients and less than or equal to 0.005% for 80 patients. Overall, undetectable MRD was achieved by 52 patients in CR1 (85%; 95% CI: 74%, 93%) and 18 patients in CR2 (72%; 95% CI: 51%, 88%). The median estimated hematological RFS with majority of patients transplanted was 35.2 (range: 0.4, 53.5) months for patients in CR1 and 12.3 (range 0.7, 42.3) months for patients in CR2.

The most common adverse reactions to blinatumomab in at least 20% of patients with MRD-positive B-cell precursor ALL were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor, and chills. Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions in at least 2% of patients included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection. Adverse reactions of Grade 3 or higher were reported in 64% of patients. Discontinuation of therapy due to adverse reactions occurred in 17% of patients; neurologic events were the most frequently reported reasons for discontinuation. There were 2 fatal adverse events that occurred within 30 days of the end of blinatumomab treatment (atypical pneumonia and subdural hemorrhage).

See Full Prescribing Information for recommended dose by patient weight and schedule: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf

FDA granted this application priority review and orphan designation. Continued approval for the new indication is contingent upon verification and description of clinical benefit in confirmatory trials. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist’s Applications to Practice

Blinatumomab for the Treatment of Adult and Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia in First or Second Complete Remission with Positive Minimal Residual Disease

Author: Morgan Randolph, PharmD BCOP
Clinical Pharmacy Specialist, Pediatric Hematology/Oncology
Children’s Hospital of Richmond at VCU
Richmond, VA

What is the potential role for blinatumomab in the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%?1-4

  • The U.S. Food and Drug Administration (FDA) granted blinatumomab accelerated approval on March 29, 2018, for the treatment of adult and pediatric patients with B-cell precursor ALL in first or second CR with MRD greater than or equal to 0.1%.
  • Blinatumomab is currently the only bispecific T-cell engager on the market and the only medication currently approved for this indication. The role of blinatumomab in this setting is primarily as a bridge to hematopoietic stem cell transplant (HSCT).
  • Prior studies have found that a detectable MRD prior to transplant is associated with a higher subsequent relapse rate. The goal of blinatumomab in this setting is to eradicate the remaining disease prior to transplant to decrease the risk of relapse. This approval was based on the results of the BLAST trial, an open-label multicenter single-arm study (N = 86).
    • Participants were at least 18 years of age, had received at least three chemotherapy blocks of standard ALL therapy, were in complete hematologic remission, and had MRD greater than or equal to 0.1%.
    • Blinatumomab was administered at a constant dose of 15 mcg/m2/day with a maximum of 28 mcg/day on days 1–28 of each cycle. A dose titration was not used in this setting because the patients were in CR and had less disease burden at the beginning of therapy.
    • Initial efficacy results revealed an undetectable MRD in 65 out of 80 total patients (81%), and the median estimated hematological relapse-free survival duration was 24.2 months.
    • A complete updated analysis (N = 113) demonstrated that 88 participants (78%) achieved a complete MRD response after cycle 1, with two additional patients achieving a complete MRD response after cycle 2. No additional patients achieved a complete MRD response after cycle 3 or cycle 4, suggesting that if no benefit is seen after cycle 2, it may be an indication to proceed with transplant or change the treatment.
      • Complete MRD response rates were similar between patients with MRD greater than or equal to 10-2 and those with MRD less than 10-2 at baseline. These results are reassuring and suggest that it could still be beneficial for patients with a higher disease burden to receive blinatumomab prior to transplant.
      • Median overall survival was 38.9 months in MRD responders versus 12.5 months in MRD nonresponders.
      • Median hematologic relapse-free survival was 23.6 months in MRD responders versus 5.7 months in MRD nonresponders, further demonstrating the impact of MRD response on patient outcomes.
  • It is important to note that the inclusion of pediatric patients in this FDA approval was based on extrapolation of data from the BLAST trial, which included only patients over 18 years of age. The safety and efficacy of blinatumomab was previously established in pediatric patients with relapsed or refractory disease in the MT103-205 trial, but not in this setting. This study included patients ranging from 7 months of age to 17 years of age.
    • Blinatumomab was administered at a dose of 5 mcg/m2/day on days 1–7 and 15 mcg/m2/day on days 8–28 for cycle 1 and 15 mcg/m2/day on days 1–28 for subsequent cycles.
    • Seventeen patients (73.9%) achieved a CR within cycle 1, and 23 patients (32.9%) achieved a CR within the first two treatment cycles.
    • No differences in efficacy between the age subgroups were noted.
  • The use of blinatumomab has been added by the National Comprehensive Cancer Network (NCCN) for the treatment of adult, adolescent, and young adult Philadelphia chromosome–negative ALL patients less than 65 years of age without substantial comorbidities once they have achieved a CR if they have MRD-positive disease. It is being considered as an alternative to upfront allogeneic HSCT. Because historical data suggest that better transplant outcomes are seen with a negative MRD prior to transplant, the option to try to achieve a negative MRD for better durable response rates is appealing.
    • The NCCN guidelines note that long-term remission after blinatumomab therapy is possible, but allogeneic HSCT should be considered as a consolidative therapy.

What role can the pharmacist play in the management of patients receiving blinatumomab?1,3-5

  • The approved dosing and schedule included in the updated prescribing information is a weight-based fixed dose on days 1–28 of each cycle followed by a 2-week rest period.
    • This dosing scheme contrasts with the dose titration used in the relapsed or refractory setting. Because these patients were in a CR prior to initiation of therapy, the risk of cytokine release syndrome (CRS) and tumor lysis syndrome is lower.
    • CRS can still occur in the setting of a CR with MRD-positive disease, but with less frequency than in the relapsed or refractory setting. CRS was reported in 15% of patients with relapsed or refractory ALL and in 7% of patients with MRD-positive ALL.
  • Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle, as compared to 9 days of the first cycle in the relapsed or refractory setting. Because the hospitalization requirement with these patients is shorter, policies and procedures may need to be updated to reflect the new recommendation or to explain the rationale for maintaining the same requirements for these patients.
  • The prescribing information recommends a slightly different glucocorticoid in this setting than that used in the relapsed or refractory setting.
    • For adults, prednisone 100 mg intravenous or equivalent (dexamethasone 16 mg) 1 hour prior to the first dose of blinatumomab in each cycle is recommended for the new indication, compared to dexamethasone 20 mg in the relapsed or refractory setting.
    • For pediatric patients, dexamethasone 5 mg/m2 (maximum dose of 20 mg) 1 hour prior to the first dose of blinatumomab is recommended in the first cycle only. No glucocorticoid is administered after the first cycle unless the toxicity level warrants it.
  • The infusion-duration options included in the prescribing information are limited to 24 hours, 48 hours, and a 7-day infusion using bacteriostatic 0.9% sodium chloride injection (containing 0.9% benzyl alcohol), at varying rates. Careful attention to detail is required by the verifying pharmacist to ensure that all dose calculations, preparation, and rates are accurate.
    • The 7-day infusion is an option only for patients weighing greater than or equal to 22 kg because of the benzyl alcohol component.
    • Depending on clinic hours and whether the clinic is closed on weekends, this schedule could pose a problem for bag changes that are not able to be done at home.
    • The prescribing information includes a chart for the infusion-bag preparation for patients weighing less than 45 kg. The amount of reconstituted blinatumomab added to the bag is adjusted based on body surface area ranges and whether the infusion will run over 24 or 48 hours. It is critical that this chart be referred to throughout the preparation process and product checking.
  • Adverse reactions
    • The most common adverse reactions occurring in greater than or equal to 20% of patients were infections, pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia.
    • The most concerning adverse reactions that can occur with blinatumomab are CRS (median time to onset was 2 days), neurological toxicities (median time to onset was 14 days), tumor lysis syndrome, elevated liver enzymes, pancreatitis, and leukoencephalopathy.
    • Adverse reactions that have been observed more in the pediatric population than in the adult population are pyrexia (80% vs. 61%), infusion-related reactions (49% vs. 34%), anemia (41% vs. 24%), thrombocytopenia (34% vs. 21%), hypertension (26% vs. 8%), leukopenia (24% vs. 11%), and increased weight (17% vs. 6%). The frequency of neurological events was no different in the pediatric population than in adults, but the signs and symptoms were different. The pediatric patients experienced agitation, headache, insomnia, somnolence, and irritability.
    • It is important to refer to the prescribing information for evaluation and management of any adverse reaction. It contains specific instructions on proceeding with treatment of symptoms, reinitiating treatment, and judging whether therapy should be discontinued on the basis of toxicity level and grade.
  • Financial assistance may be available for privately insured, Medicare, and uninsured patients. More information can be found by calling 1.888.427.7478 or visiting www.amgenassist360.com.

Clinical Pearls1-7

  • It is important to note that the 7-day infusion runs at a rate of only 0.6 ml/hour. This allows patients to have only one infusion pump because the infusion rate is constant throughout the week and only one bag change is needed.
  • The prescribing information includes storage requirements for the reconstituted blinatumomab vial, the preservative-free blinatumomab infusion bag, and the infusion bag containing blinatumomab with preservative. The information specifies the length of time that these can be stored at room temperature and while refrigerated. It is important to note that the storage time includes the infusion time. If the prepared blinatumomab infusion bag is not administered within the time frames and temperature indicated, then it must be discarded. This is very important for 48-hour infusions, because the designated maximum storage time is also 48 hours at room temperature.
  • Induction and consolidation cycles consist of a continuous 28-day infusion of blinatumomab. It is important to note that, depending on the infusion bags used throughout treatment, hanging an additional 24-hour bag on day 28 may be necessary in order to administer the full 28 days of therapy. This is followed by a 14-day rest period prior to the next cycle.

References

  1. U.S. Food and Drug Administration. FDA granted accelerated approval to blinatumomab (Blincyto, Amgen Inc.) for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm603171.htm. Accessed May 15, 2018.
  2. Topp MS, Gökbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood.2012;120(26):5185-5187.
  3. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood.2018;131(14):1522-1531.
  4. Von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol.2016;34:4381-4389.
  5. Blinatumomab (Blincyto) [package insert]. Thousand Oaks, CA: Amgen Inc.; revised March 2018.
  6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia. Version 1.2018. Available at https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed May 15, 2018.
  7. Gore L, Locatelli F, Zugmaier, et al. Initial results from a phase 2 study of blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood.2014;124:3703.

July 11, 2017, with PAP

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125557s008lbl.pdf

On July 11, 2017, the U.S. Food and Drug Administration approved blinatumomab (BLINCYTO®, Amgen Inc.) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

Blinatumomab received accelerated approval in December 2014 for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. This current supplement provides the confirmation of clinical benefit required under the accelerated approval and also expands the indication to include Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL.

The trial that confirmed clinical benefit was a randomized, open label, multicenter clinical trial (TOWER, NCT02013167), comparing blinatumomab to standard-of-care (SOC) chemotherapy in 405 patients with relapsed or refractory B-cell precursor ALL. Blinatumomab was administered at 9 mcg/day on days 1 7 and 28 mcg/day on days 8 28 for cycle 1 in a 42-day cycle, at 28 mcg/day on days 1 28 for cycles 2 5 in 42 day cycles, and at 28 mcg/day on days 1 28 for cycles 6 9 in 84 day cycles. The trial demonstrated a statistically significant improvement in overall survival (OS) for patients treated with blinatumomab compared to those treated with SOC (hazard ratio 0.71; 95% CI: 0.55, 0.93, p=0.012). The estimated median OS was 7.7 months in the blinatumomab arm (95% CI: 5.6, 9.6) and 4.0 months in the SOC arm (95% CI: 2.9, 5.3). An independent data monitoring committee recommended that the study end early for efficacy based upon these results that were prespecified in an interim analysis.

The inclusion of Philadelphia chromosome-positive relapsed or refractory B cell precursor ALL in the indication was based on a single-arm, multicenter study (ALCANTARA, NCT02000427) enrolling 45 patients with Philadelphia chromosome-positive ALL. Patients either had disease resistant to second generation tyrosine kinase inhibitors or were intolerant to second generation tyrosine kinase inhibitors and had disease resistant to imatinib. In this population, 36% of the patients achieved a complete remission with complete or partial hematological recovery. The median duration of remission was 6.7 months.

No new major adverse reactions of blinatumomab were identified in the above clinical trials. Dosage and administration schedule of blinatumomab is based on weight for patients weighing <45 kg and fixed dose for those ≥45 kg. Patients should be premedicated with dexamethasone. Hospitalization is recommended at the beginning of the first and second cycles. Details are available in the full prescribing information:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125557s008lbl.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist’s Applications to Practice

Blinatumomab for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in Adults and Children

Author: Morgan Culver, PharmD BCOP
Clinical Pharmacy Specialist, Hematology/Oncology
VCU Health
Richmond, VA

What is the potential role for blinatumomab in the treatment of relapsed or refractory (RR) B-cell precursor acute lymphoblastic leukemia (ALL)?1-4

  • The U.S. Food and Drug Administration (FDA) granted blinatumomab accelerated approval in December 2014 for RR B-cell precursor ALL in patients who were Philadelphia chromosome–negative (Ph-). The updated approval on July 11, 2017, validates the benefit as required via the accelerated approval process and expands the indication to include the treatment of Philadelphia chromosome–positive (Ph+) ALL.
    • The confirmatory data were based on interim analysis results from the prospective, randomized, phase 3, TOWER trial in Ph- patients who had received at least one prior line of therapy (N = 405). The study was stopped early because of an overall survival benefit of 7.7 months with blinatumomab versus 4 months with standard-of-care chemotherapy, as chosen by the investigators (hazard ratio = .71, 95% confidence interval = .55–.93, p = .012). Investigators could choose between fludarabine + cytarabine + granulocyte colony stimulating factor + idarubicin (FLAG + Ida), a high-dose cytarabine-based regimen, a high-dose methotrexate-base regimen, or a clofarabine-based regimen. Complete remission (CR) rates were also significantly higher with blinatumomab as compared to standard-of-care chemotherapy (34% vs. 16%, respectively).
    • The expanded indication to the Ph+ population was granted as a result of the open-label, phase 2, ALCANTARA study (N = 45), which demonstrated a CR rate of 36% in participants, all of whom were refractory or intolerant to second-generation tyrosine kinase inhibitors (TKIs) and imatinib. Patients appeared to respond regardless of how many TKIs they had been exposed to previously or whether they had received ponatinib.
  • Blinatumomab is currently the only bispecific T-cell engager (BiTE) on the market and the only drug of its kind approved for ALL, in either Ph+ or Ph- patients.
  • Blinatumomab provides an additional option in the RR setting and has received the only category 1 recommendation by the National Comprehensive Cancer Network in this setting.
    • It can be considered in those patients who are not ideal candidates for intensive multi-agent chemotherapy.
    • For Ph+ patients, where relatively few options currently exist, blinatumomab should be considered in patients who have failed treatment with at least two TKIs, regardless of T315I status.

What role can the pharmacist play in the management of patients on blinatumomab?5

  • Given the variations in dosing and durations of infusion (24- and 48-hour infusions and 7-day infusions), pharmacists should be highly vigilant when verifying orders and products prepared for administration.
    • A dose titration starting at 9 mcg per day for the first 7 days and then escalating to 28 mcg per day is required during the initial induction cycle to mitigate the risk of capillary leak syndrome. All other cycles are administered at a flat dose of 28 mcg per day for patients weighing 45 kg or more. Weight-based dosing is recommended for patients weighing less than 45 kg.
    • Blinatumomab should be infused via low-protein binding, polyvinyl chloride/di(2-ethylhexyl) phthalate (PVC/DEHP)–free tubing with an in-line filter at a flat rate, as determined                      on the basis of the dose and infuse-over time. The rate should not be increased for any reason, and the line should not be flushed at any time during administration or between bag changes.
    • The prepared volume is more than the volume administered to the patient; therefore, some medication will remain in the prepared bag following the completion of the infusion. This should be discarded when the designated infusion time has elapsed.
  • Patients should be premedicated with dexamethasone prior to blinatumomab initiation and dose titrations and when the infusion is delayed more than 4 hours.
  • Prophylactic antimicrobials are recommended because of the increased risk of infection associated with blinatumomab.
  • If possible, disease burden should be decreased, and aggressive hydration is recommended prior to the start of treatment to decrease the risk of tumor lysis syndrome.
  • Patients should be warned to avoid driving or operating heavy machinery while receiving blinatumomab.
  • A temporary elevation of cytokines following blinatumomab initiation may result in inhibition of CYP450 enzymes. Although no formal drug interaction studies have been performed, it is theorized that the greatest risk of interaction with CYP450 substrates would occur during the first 9 days of the initial cycle and the first 2 days of the second cycle.
  • In the event of an adverse reaction, particularly cytokine release syndrome or a neurologic event, consult the prescribing information for details regarding hold parameters and reinitiation.
    • Corticosteroids such as methylprednisolone and anti-epileptics such as levetiracetam should be readily available during the initiation of blinatumomab and following the initial dose escalation.
    • Approximately two-thirds of patients experienced a neurologic event, with a median time to the first event occurring around 2 weeks after the start of the first cycle. The majority of events were mild; however, 13% experienced grade 3 or higher neurologic events, most of which resolved with discontinuation of blinatumomab.

Clinical Pearls2,3,5,6

  • Based on a subgroup analysis in the TOWER study, a significant difference in CR rates in favor of blinatumomab was found across all groups; however, the overall survival benefit was primarily seen in those receiving first or second salvage therapy. The following factors were not significant predictors of survival: age greater than or equal to 35 years or less than 35 years; third or later salvage; history of allogeneic transplant; or greater than or equal to 50% blasts or less than 50% blasts.
  • Of the 10 patients in the ALCANTARA study who had a documented T315I mutation, 40% responded to blinatumomab, including achievement of complete minimal residual disease response.
  • Induction, consolidation, and continuation cycles consist of a 28-day continuous infusion. This is followed by a 14-day treatment-free period during induction and consolidation and a 56-day treatment-free period during continuation.
    • It is recommended that patients be admitted to an inpatient setting for the first 9 days of the initial cycle and the first 2 days of the second cycle.
  • Financial assistance may be available for privately insured, Medicare, and uninsured patients. More information can be found by calling 1.888.427.7478 or visiting www.amgenassist360.com.
  • In the event of grade 3-4 cytokine release syndrome, tocilizumab, an interleukin-6 receptor antagonist, may be considered.
  • Patients with known central nervous system disease were excluded from clinical trials.

References

  1. Blinatumomab. U.S. Food and Drug Administration: Approved Drugs. July 11, 2017. Available at: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566708.htm. Accessed August 10, 2017.
  2. Kantarjian H, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847.
  3. Martinelli G, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802.
  4. Acute Lymphoblastic Leukemia. Version 1.2017. National Comprehensive Cancer Network. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed August 10, 2017.
  5. Blincyto (blinatumomab) [package insert]. Thousand Oaks, CA: Amgen Inc.; July 2017.
  6. Teachey DT, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013;121:5154-5157.
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